Cephalic phase of insulin secretion is regulated by autonomic and endocrine responses to food-related sensory stimulation such as sight, smell, and taste. Human taste perception comprises of at least five distinct qualities: bitterness, saltiness, sourness, sweetness, and umami, the sensation elicited by glutamate, commonly found in protein (meat, fish, and legumes) and flavor enhancer such as monosodium glutamate (MSG). Both the sweet and umami taste stimuli had been shown to illicit cephalic-phase insulin release in rats. Oral sensory stimulation in human with modified sham feeding (MSF where food is smelled, chewed, but not swallowed) had been shown to enhance insulin release during the cephalic phase, lower postprandial glucose level, and improve glucose tolerance in healthy subjects. The loss of pre-absorptive insulin response has been shown to impair glucose tolerance. Furthermore, patients with type 2 diabetes and their first degree relatives had been shown to have impairment of sweet taste. We have determined that glucose stimulates glucagon-like peptide-1 (GLP-1) through activation of sweet receptors in L cells. The L cells are the specialized cells of the gut that contain GLP-1, and sweet receptors were thought to be present only on tast cells within taste buds. Recently, we found that GLP-1 and peptide YY (PYY) are prsent in the taste cells located in the taste buds of mice. These new findings raise several interesting questions of whether strict tasting of food without ingestion may stimulate secretion of GLP-1 and PYY from the taste cells, whether their secretion is involved in the afferent input of the cranial nerves, and whether this secretion is impaired in obesity and in patients with pre-diabetes or type 2 diabetes. We also want to investigate whether different tastants, such as sweet versus umami, and different food contents such as percent fat versus carbohydrate compositions, would elicit different hormonal responses. More recently, we have ascertained that insulin is the trophic factor responsible for maintaining taste cell number and taste bud size. We are presently working on (1) hyperactivating the insulin receptor and (2) eliminating locally produced insulin in taste buds. Hopefully these type of experiments should elucidate clearly the requirement of insulin for taste cell proliferation and differentiation.